FDA approves ripretinib as fourth-line treatment for GIST
The FDA has approved ripretinib tablets for the treatment of advanced gastrointestinal stromal tumor, or GIST, in the fourth-line setting.
Ripretinib (Qinlock; Deciphera Pharmaceuticals, Inc.) is the first new drug specifically approved for fourth-line treatment of GIST. It was approved for use in adult patients who have been treated previously with three or more kinase inhibitor therapies, including imatinib, according to the FDA.
The approval was based on data from the phase 3 INVICTUS study, which evaluated the impact of ripretinib compared with placebo on PFS among patients with advanced GIST who had received prior treatment with imatinib, sunitinib (Sutent, Pfizer) and regorafenib (Nexavar, Bayer). According to a press release on the approval, average PFS in patients who received ripretinib was 6.3 months compared with 1 month for patients who received placebo.
Researchers randomly assigned patients 2:1 to ripretinib dosed at 150 mg or placebo once daily. PFS as determined by independent radiologic review served as the primary endpoint. Secondary endpoints included objective response rate and OS.
Results showed patients who received ripretinib achieved considerably longer median PFS compared with those assigned placebo (6.3 months vs. 1 month; HR = 0.15; P < .0001).
Researchers also observed a higher ORR (9.4% vs. 0%) and longer median OS (15.1 months vs. 6.6 months; HR = 0.36) in the ripretinib group.
“[This] approval of Qinlock establishes a new standard of care for patients who have received three prior therapies,” Margaret von Mehren, MD, chief of sarcoma oncology and associate director for clinical research at Fox Chase Cancer Center, said in a Deciphera-issued press release. “GIST is a complex disease and the majority of patients who initially respond to traditional tyrosine kinase inhibitors eventually develop tumor progression due to secondary mutations. In the INVICTUS study, Qinlock has demonstrated compelling clinical benefit in [PFS and OS]. Qinlock is well-tolerated and is a crucial new therapy for these patients with a high unmet need.”
The most commonly reported side effects in the ripretinib arm included alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome and vomiting.
Eight percent of ripretinib-treated patients discontinued treatment due to adverse events, 24% required dosage interruptions and 7% required dose reductions.
GIST, a tumor that originates in the gastrointestinal tract, is diagnosed in approximately 4,000 to 6,000 adults In the United States each year.
“Despite the progress that has been made over the past 20 years in developing treatments for GIST, including four FDA-approved targeted therapies, some patients don’t respond to treatment and their tumors continues to progress,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in the release. “Today’s approval provides a new treatment option for patients who have exhausted all FDA-approved therapies for GIST.”
The FDA previously granted breakthrough therapy, fast track and priority review designations to ripretinib for this indication.
“The FDA approval of Qinlock is an exciting milestone for people with GIST who have been waiting for a new treatment option designed specifically for their disease,” Steve Hoerter, president and CEO of Deciphera, said in the company-issued release.